tbuckley/cabot-search huggingface dataset:
Standard vs Augmented Ablation of Paroxysmal Atrial Fibrillation for Reduction of Atrial Fibrillation Recurrence
Authors: Girish M. Nair, David H. Birnie, Pablo B. Nery, Calum J. Redpath, Jean-Francois Sarrazin, Jean-Francois Roux, Ratika Parkash, Martin Bernier, Laurence D. Sterns, John Sapp, Paul Novak, George Veenhuyzen, Carlos A. Morillo, Sheldon M. Singh, Mouhannad M. Sadek, Mehrdad Golian, Andres Klein, Marcio Sturmer, Vijay S. Chauhan, Paul Angaran, Martin S. Green, Jordan Bernick, George A. Wells, Vidal Essebag
Journal: JAMA Cardiology (2023)

Recurrent atrial fibrillation (AF) commonly occurs after catheter ablation and is associated with patient morbidity and health care costs.
Cell-Autonomous Cxcl1 Sustains Tolerogenic Circuitries and Stromal Inflammation via Neutrophil-Derived TNF in Pancreatic Cancer
Authors: Anna Bianchi, Iago De Castro Silva, Nilesh U. Deshpande, Samara Singh, Siddharth Mehra, Vanessa T. Garrido, Xinyu Guo, Luis A. Nivelo, Despina S. Kolonias, Shannon J. Saigh, Eric Wieder, Christine I. Rafie, Austin R. Dosch, Zhiqun Zhou, Oliver Umland, Haleh Amirian, Ifeanyichukwu C. Ogobuiro, Jian Zhang, Yuguang Ban, Carina Shiau, Nagaraj S. Nagathihalli, Elizabeth A. Montgomery, William L. Hwang, Roberta Brambilla, Krishna Komanduri, Alejandro V. Villarino, Eneda Toska, Ben Z. Stanger, Dmitry I. Gabrilovich, Nipun B. Merchant, Jashodeep Datta
Journal: Cancer Discovery (2023)

Abstract We have shown that KRAS–TP53 genomic coalteration is associated with immune-excluded microenvironments, chemoresistance, and poor survival in pancreatic ductal adenocarcinoma (PDAC) patients. By treating KRAS–TP53 cooperativity as a model for high-risk biology, we now identify cell-autonomous Cxcl1 as a key mediator of spatial T-cell restriction via interactions with CXCR2+ neutrophilic myeloid-derived suppressor cells in human PDAC using imaging mass cytometry. Silencing of cell-intrinsic Cxcl1 in LSL-KrasG12D/+;Trp53R172H/+;Pdx-1Cre/+(KPC) cells reprograms the trafficking and functional dynamics of neutrophils to overcome T-cell exclusion and controls tumor growth in a T cell–dependent manner. Mechanistically, neutrophil-derived TNF is a central regulator of this immunologic rewiring, instigating feed-forward Cxcl1 overproduction from tumor cells and cancer-associated fibroblasts (CAF), T-cell dysfunction, and inflammatory CAF polarization via transmembrane TNF–TNFR2 interactions. TNFR2 inhibition disrupts this circuitry and improves sensitivity to chemotherapy in vivo. Our results uncover cancer cell–neutrophil cross-talk in which context-dependent TNF signaling amplifies stromal inflammation and immune tolerance to promote therapeutic resistance in PDAC. Significance: By decoding connections between high-risk tumor genotypes, cell-autonomous inflammatory programs, and myeloid-enriched/T cell–excluded contexts, we identify a novel role for neutrophil-derived TNF in sustaining immunosuppression and stromal inflammation in pancreatic tumor microenvironments. This work offers a conceptual framework by which targeting context-dependent TNF signaling may overcome hallmarks of chemoresistance in pancreatic cancer. This article is highlighted in the In This Issue feature, p. 1275
Trial of intravenous immunoglobulin in dermatomyositis: a critically appraised research paper
Authors: Rachita Pandya, Julianne Kleitsch, Victoria P Werth
Journal: British Journal of Dermatology (2023)

Aggarwal et al. recently reported results from the first successful phase III trial studying intravenous immunoglobulin (IVIG) in dermatomyositis (DM). The study showed that improvement in disease activity was clinically and statistically significantly greater in those who received IVIG than in those who received placebo, allowing US Food and Drug Administration approval for use of IVIG in DM. Despite its success, this study also highlights several concerns that must be addressed to inform future trials in the field, particularly the inclusion of patients with skin-predominant/amyopathic and post-myopathic DM.
Transposable Element Interactions Shape the Ecology of the Deer Mouse Genome
Authors: Landen Gozashti, Cedric Feschotte, Hopi E Hoekstra
Journal: Molecular Biology and Evolution (2023)

Abstract The genomic landscape of transposable elements (TEs) varies dramatically across species, with some TEs demonstrating greater success in colonizing particular lineages than others. In mammals, long interspersed nuclear element (LINE) retrotransposons are typically more common than any other TE. Here, we report an unusual genomic landscape of TEs in the deer mouse, Peromyscus maniculatus. In contrast to other previously examined mammals, long terminal repeat elements occupy more of the deer mouse genome than LINEs (11% and 10%, respectively). This pattern reflects a combination of relatively low LINE activity and a massive invasion of lineage-specific endogenous retroviruses (ERVs). Deer mouse ERVs exhibit diverse origins spanning the retroviral phylogeny suggesting they have been host to a wide range of exogenous retroviruses. Notably, we trace the origin of one ERV lineage, which arose ∼5–18 million years ago, to a close relative of feline leukemia virus, revealing inter-ordinal horizontal transmission. Several lineage-specific ERV subfamilies have very high copy numbers, with the top five most abundant accounting for ∼2% of the genome. We also observe a massive amplification of Kruppel-associated box domain-containing zinc finger genes, which likely control ERV activity and whose expansion may have been facilitated by ectopic recombination between ERVs. Finally, we find evidence that ERVs directly impacted the evolutionary trajectory of LINEs by outcompeting them for genomic sites and frequently disrupting autonomous LINE copies. Together, our results illuminate the genomic ecology that shaped the unique deer mouse TE landscape, shedding light on the evolutionary processes that give rise to variation in mammalian genome structure.
Courts’ Disregard for Women’s Health and Safety — Intimate Partner Violence, Firearms, and “History and Tradition”
Authors: Elizabeth Tobin-Tyler
Journal: New England Journal of Medicine (2023)

Interview with Prof. Elizabeth Tobin-Tyler on recent court decisions related to gun possession by people subject to certain types of restraining orders. (11:52)Download Decisions by two federal courts could endanger people who have experienced intimate partner violence and demonstrate the consequences of a new approach to interpreting the Second Amendment.
Shorter sleep time relates to lower human defensin 5 secretion and compositional disturbance of the intestinal microbiota accompanied by decreased short-chain fatty acid production
Authors: Yu Shimizu, Ryodai Yamamura, Yuki Yokoi, Tokiyoshi Ayabe, Shigekazu Ukawa, Koshi Nakamura, Emiko Okada, Akihiro Imae, Takafumi Nakagawa, Akiko Tamakoshi, Kiminori Nakamura
Journal: Gut Microbes (2023)

Sleep is essential for our health. Short sleep is known to increase disease risks via imbalance of intestinal microbiota, dysbiosis. However, mechanisms by which short sleep induces dysbiosis remain unknown. Small intestinal Paneth cell regulates the intestinal microbiota by secreting antimicrobial peptides including α-defensin, human defensin 5 (HD5). Disruption of circadian rhythm mediating sleep-wake cycle induces Paneth cell failure. We aim to clarify effects of short sleep on HD5 secretion and the intestinal microbiota. Fecal samples and self-reported sleep time were obtained from 35 healthy middle-aged Japanese (41 to 60-year-old). Shorter sleep time was associated with lower fecal HD5 concentration (r = 0.354, p = 0.037), lower centered log ratio (CLR)-transformed abundance of short-chain fatty acid (SCFA) producers in the intestinal microbiota such as [Ruminococcus] gnavus group (r = 0.504, p = 0.002) and Butyricicoccus (r = 0.484, p = 0.003), and lower fecal SCFA concentration. Furthermore, fecal HD5 positively correlated with the abundance of these genera and SCFA concentration. These findings suggest that short sleep relates to disturbance of the intestinal microbiota via decreased HD5 secretion.
Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood
Authors: Laura Maintz, Marie‐Therese Schmitz, Nadine Herrmann, Svenja Müller, Regina Havenith, Juliette Brauer, Claudio Rhyner, Anita Dreher, Eugen Bersuch, Danielle Fehr, Gertrud Hammel, Matthias Reiger, Daria Luschkova, Avidan Neumann, Claudia C. V. Lang, Ellen D. Renner, Peter Schmid‐Grendelmeier, Claudia Traidl‐Hoffmann, Cezmi A. Akdis, Roger Lauener, Marie‐Charlotte Brüggen, Matthias Schmid, Thomas Bieber
Journal: Allergy (2023)

Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls.We analyzed cross-sectional data of the CK-CARE-ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood-onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult-onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non-atopic)).We identified active smoking to be associated with adult-onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06-29.01] vs. controlsnon-atopic , aOR = 4.03 [1.20-13.45] vs. controlsatopic ). Conjunctivitis showed a negative association versus controlsatopic (aOR = 0.36 [0.14-0.91]). Food allergy (aOR = 2.93 [1.44-5.96]), maternal food allergy (aOR = 9.43 [1.10-80.95]), palmar hyperlinearity (aOR = 2.11 [1.05-4.25]), and academic background (aOR = 2.14 [1.00-4.54]) increased the odds of childhood-onset AD versus controlsatopic . Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12-4.13]), but reduced odds to feature multiple (3-4) atopic comorbidities (aOR = 0.34 [0.14-0.84]). Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in "high-atopic"-clusters.The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors.
Estimating Cancer Treatment Tolerability for Older Adults With Advanced Cancer—The Holy Grail
Authors: Carolyn J. Presley
Journal: JAMA Network Open (2023)

Huiwen Xu, PhD, MHA; Mostafa Mohamed, MBBCh; Marie Flannery, PhD, RN; Luke Peppone, PhD; Erika Ramsdale, MD, MS; Kah Poh Loh, MBBCh, BAO, MS; Megan Wells, MPH; Leah Jamieson, RN; Victor G. Vogel, MD; Bianca Alexandra Hall, BA; Karen Mustian, PhD, MPH; Supriya Mohile, MD, MS; Eva Culakova, PhD, MS
The association between atopic dermatitis and acne: a retrospective Finnish nationwide registry study
Authors: Suvi-Päivikki Sinikumpu, Jari Jokelainen, Laura Huilaja
Journal: British Journal of Dermatology (2023)

Hospital-diagnosed acne was more common in patients with atopic dermatitis (AD) than in controls. Moreover, the frequency of hospital-diagnosed acne was greater in patients who received more potent AD treatments. The increased risk of acne in patients with AD should be considered by physicians treating patients with AD.
<i>JAMA Cardiology</i>—The Year in Review, 2022
Authors: Robert O. Bonow
Journal: JAMA Cardiology (2023)

In our annual review of JAMA Cardiology, I am pleased to report that 2022 marked another year of steady growth in publishing original science, reviews, and opinion articles covering the areas of cardiology of interest to our readers.We received 2279 manuscripts (Table ), including 1832 original science submissions, which is comparable to prepandemic submissions in 2019.Submissions related to the pandemic and its cardiovascular ramifications totaled 118 (7.9% of total submissions), compared with 12.3% in 2021 and 24.7% in 2020.JAMA Cardiology continues to be a global journal with more than 60% of submissions arriving from outside the US.The journal's acceptance rate of 6% for original science manuscripts is on par with that of the other major journals in our field.The continuous flow of manuscripts adds to the workload of our very busy editors, but we relish the new knowledge and opinions that we see, evaluate, and discuss each week in our manuscript review meeting.We continue to learn from each other and our authors, peer reviewers, 7 and colleagues around the world.JAMA Cardiology's impact factor was 30.2 in 2022 (which is reported for 2021).The journal's weekly online content is now delivered to more than 97 000 readers, with 3.3 million annual article views and downloads.We maintain an active presence on social media, with an increase during the past year to more than 114 000 Twitter and Facebook followers.The JAMA Cardiology monthly podcast 8 discussions with authors remain highly popular.The close linkage of this journal to JAMA and the other JAMA Network journals connects us to the dedicated editorial and publication staff who facilitate the dissemination of the journal's content each week and amplify the reach of published content through multimedia, social media, and news media channels.Articles published in JAMA Cardiology in 2022 received mention in more than 7000 news reports.It is difficult this early in the new year to recognize which manuscripts published in 2022 will ultimately have the greatest impact, but we can identify those that received the most views and downloads, the highest Altmetric scores (measures of news and social media coverage), and the greatest number of citations in 2022 (Table ).The most notable of these was the study by Karlstad et al 1 examining the incidence of myocarditis diagnoses associated with vaccination for COVID-19 among 23.1 million individuals in the 4 Nordic countries.This report indicated that the incidence of myocarditis following administration of a messenger RNA (mRNA) vaccine was highest in male individuals aged 16 to 24 years, particularly after the second dose.But even in this highest-risk group, the incidence of myocarditis was low, estimated to be 5.5 events per 100 000 persons after the second dose of BNT162b2 and 18.4 events per 100 000 persons after the second dose of mRNA-1273.These findings confirmed the ongoing surveillance data from the US Centers for Disease Control and Prevention.Table.
Crohn’s disease-associated AIEC inhibiting intestinal epithelial cell-derived exosomal let-7b expression regulates macrophage polarization to exacerbate intestinal fibrosis
Authors: Yihan Xu, Wenwei Qian, Liangyu Huang, Weiwei Wen, Yi Li, Feilong Guo, Zhenxing Zhu, Zhun Li, Jianfeng Gong, Zeqian Yu, Yan Zhou, Nan Lu, Weiming Zhu, Zhen Guo
Journal: Gut Microbes (2023)

The interaction between adherent-invasive Escherichia coli (AIEC) and intestinal macrophages is implicated in the pathogenesis of Crohn's disease (CD). However, its role in intestinal fibrogenesis and the underlying molecular mechanisms are poorly understood. In addition, miRNAs such as let-7b may participate in AIEC-macrophage interactions. In this study, we identified that the colonization of AIEC in the ileum was associated with enhanced intestinal fibrosis and reduced let-7b expression by enrolling a prospective cohort of CD patients undergoing ileocolectomy. Besides, AIEC-infected IL-10−/− mice presented more severe intestinal fibrosis and could be improved by exogenous let-7b. Mechanistically, intestinal macrophages were found to be the main target of let-7b. Transferring let-7b-overexpressing macrophages to AIEC-infected IL-10−/− mice significantly alleviated intestinal fibrosis. In vitro, AIEC suppressed exosomal let-7b derived from intestinal epithelial cells (IECs), instead of the direct inhibition of let-7b in macrophages, to promote macrophages to a fibrotic phenotype. Finally, TGFβR1 was identified as one target of let-7b that regulates macrophage polarization. Overall, the results of our work indicate that AIEC is associated with enhanced intestinal fibrosis in CD. AIEC could inhibit exosomal let-7b from IECs to promote intestinal macrophages to a fibrotic phenotype and then contributed to fibrogenesis. Thus, anti-AIEC or let-7b therapy may serve as novel therapeutic approaches to ameliorate intestinal fibrosis.
Leveraging electronic medical record-embedded standardised electroencephalogram reporting to develop neonatal seizure prediction models: a retrospective cohort study
Authors: Jillian L McKee, Michael C Kaufman, Alexander K Gonzalez, Mark P Fitzgerald, Shavonne L Massey, France Fung, Sudha K Kessler, Stephanie Witzman, Nicholas S Abend, Ingo Helbig
Journal: The Lancet Digital Health (2023)
Factors associated with enrolment into a national COVID-19 pulse oximetry remote monitoring programme in England: a retrospective observational study
Authors: Jonathan Clarke, Thomas Beaney, Ahmed Alboksmaty, Kelsey Flott, Hutan Ashrafian, Aidan Fowler, Jonathan R Benger, Paul Aylin, Sarah Elkin, Ana Luisa Neves, Ara Darzi
Journal: The Lancet Digital Health (2023)
On the importance and challenges of global access to proven life-saving treatments for Ebolavirus – Authors' reply
Authors: Els Torreele, Yap Boum, Ismael Adjaho, Franck Guy Biaou Alé, Sal Ha Issoufou, Geza Harczi, Chibuzo Okonta, Piero Olliaro
Journal: The Lancet Infectious Diseases (2023)
Wearable health data privacy
Authors: None The Lancet Digital Health
Journal: The Lancet Digital Health (2023)

Wearable health-care technology has traditionally been used to monitor and improve the personal fitness of the wearer. More recently, wearables have been used by researchers in health-care research to record uniquely continuous, longitudinal health data outside of clinical settings. Data collected from wearables has been used in a plethora of research applications; from predicting COVID-19 diagnosis to surveilling influenza in real time. This month's issue of The Lancet Digital Health includes a systematic review by Chikwetu and colleagues, who aimed to provide an overview on reidentification risks of deidentified data from wearable devices, which represents a potential loss of privacy to personal and sometimes sensitive medical information.
Understanding the involvement of innate immunity and the Nrf2-NLRP3 axis on mitochondrial health in Parkinson's disease
Authors: Shruti Rajan, Kamatham Pushpa Tryphena, Sabiya Khan, Lalitkumar Vora, Saurabh Srivastava, Shashi Bala Singh, Dharmendra Kumar Khatri
Journal: Ageing Research Reviews (2023)
Estimated impact from the withdrawal of primary care financial incentives on selected indicators of quality of care in Scotland: controlled interrupted time series analysis
Authors: Daniel R Morales, Mark Minchin, Evangelos Kontopantelis, Martin Roland, Matt Sutton, Bruce Guthrie
Journal: BMJ (2023)

To determine whether the withdrawal of the Quality and Outcomes Framework (QOF) scheme in primary care in Scotland in 2016 had an impact on selected recorded quality of care, compared with England where the scheme continued.Controlled interrupted time series regression analysis.General practices in Scotland and England.979 practices with 5 599 171 registered patients in Scotland, and 7921 practices with 56 270 628 registered patients in England in 2013-14, decreasing to 864 practices in Scotland and 6873 in England in 2018-19, mainly due to practice mergers.Changes in quality of care at one year and three years after withdrawal of QOF financial incentives in Scotland at the end of the 2015-16 financial year for 16 indicators (two complex processes, nine intermediate outcomes, and five treatments) measured annually for financial years from 2013-14 to 2018-19.A significant decrease in performance was observed for 12 of the 16 quality of care indicators in Scotland one year after QOF was abolished and for 10 of the 16 indicators three years after QOF was abolished, compared with England. At three years, the absolute percentage point difference between Scotland and England was largest for recording (by tick box) of mental health care planning (-40.2 percentage points, 95% confidence interval -45.5 to -35.0) and diabetic foot screening (-22.8, -33.9 to -11.7). Substantial reductions were, however, also observed for intermediate outcomes, including blood pressure control in patients with peripheral arterial disease (-18.5, -22.1 to -14.9), stroke or transient ischaemic attack (-16.6, -20.6 to -12.7), hypertension (-13.7, -19.4 to -7.9), diabetes (-12.7, -15.0 to -12.4), or coronary heart disease (-12.8, -14.9 to -10.8), and for glycated haemoglobin control in people with HbA1c levels ≤75 mmol/mol (-5.0, -8.4 to -1.5). No significant differences were observed between Scotland and England for influenza immunisation and antiplatelet or anticoagulant treatment for coronary heart disease three years after withdrawal of incentives.The abolition of financial incentives in Scotland was associated with reductions in recorded quality of care for most performance indicators. Changes to pay for performance should be carefully designed and implemented to monitor and respond to any reductions in care quality.
Optimized Cingulate Island Sign in Discriminating Dementia With Lewy Bodies From Alzheimer Disease
Authors: Jingjie Ge, Huamei Lin, Keliang Chen, Min Wang, Zhijie He, Jiaying Lu, Zizhao Ju, Yimin Sun, Fengtao Liu, Yihui Guan, Qianhua Zhao, Chuantao Zuo, Ping Wu
Journal: Clinical Nuclear Medicine (2023)

This study aimed to optimize the analysis of cingulate island sign (CIS) to improve its diagnostic accuracy in discriminating dementia with Lewy bodies (DLB) from Alzheimer disease (AD).Patients with DLB (n = 80), AD (n = 75), and normal controls (n = 22) with 18 F-FDG PET imaging were enrolled in this study. Sixty-two DLB patients also underwent dopaminergic PET scans. The optimized/conventional CIS ratios and metabolism in associated brain regions were evaluated by diagnostic accuracy among groups and correlation with cognitive/dopaminergic dysfunction.In discriminating DLB from AD, the optimized CIS ratio calculated by dorsal posterior cingulate cortex (PCC)/lateral occipital lobe metabolism achieved the highest specificity, sensitivity, and accuracy at 0.907, 0.750, and 0.825, respectively. The metabolism of dorsal-PCC positively correlated with cognitive impairment in DLB patients cross-sectionally and longitudinally ( P < 0.001, r = 0.601; P = 0.044, r = 0.645), and also correlated with dopaminergic impairment in the caudate ( P = 0.048, r = 0.315).Optimized CIS ratios of incorporated metabolic activity of dorsal-PCC and occipital subregions are clinically useful for differentiating DLB from AD, in which dorsal-PCC metabolism may provide an objective biomarker to reflect the severity of cognitive impairment in DLB.